This K award proposal encompasses training and research experiences designed to allow Dr. Rundle to develop into an independent researcher focusing on physical activity, and cancer epidemiology. The training component includes mentored work in physical activity and lifestyle risk factor epidemiology, lung cancer epidemiology, clinical aspects of lung cancer, and the use of biomarkers as intermediate endpoints. In addition, the plan includes biostatistics coursework, participation in seminar series and conferences, and trips to receive training at other institutions doing physical activity research. The proposed research includes a case-control study that will investigate whether physical activity, is protective against lung cancer, and a cross-sectional study that uses biomarkers as intermediate endpoints to investigate the mechanisms by which physical activity may act. The case-control study will follow up on cohort and case-control studies that have shown a protective effect of physical activity on lung cancer development and has the strength of more in depth life-time measures of physical activity and smoking habits. Furthermore, the study will be the first to control for diet as a potential confounder. Of particular interest is the affect of physical activity after smoking cessation and whether this has a protective effect. The biomarker study responds to calls for biomarker studies that can help to elucidate the protective mechanisms of physical activity. Such studies may provide biological support for observed associations with cancer, and will contribute information to determine the type, frequency, and duration of exercise needed for maximum protection. The study will determine whether physical activity is associated with increased levels of glutathione and extracellular glutathione peroxidase, and whether in turn these markers are associated with lower levels of PAH-DNA adducts and oxidative damage. Both projects are directed at the development of new lung cancer prevention programs that can supplement current smoking prevention and cessation programs.